Vera Lúcia Gil-da-Silva-Lopes(a)
Isabella Lopes Monlleó(b)
(a) Department of Medical Genetics, Faculty of
Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil.
(b) Clinical Genetics Service, University
Hospital, Medical Genetics Sector, Faculty of Medicine, Federal University of Alagoas - UFAL, Maceió, AL Brazil.
Corresponding Author:
Vera Lúcia Gil-da-Silva-Lopes E-mail: [email protected]
Risk factors and the prevention of
oral clefts
Abstract: This article presents general aspects of risk factors and par-ticularities of the management of individuals with oral clefts (OCs). A practical manual of prevention and management of this congenital defect was prepared based on a review of the literature and using data from Brazilian multicenter studies. Since OCs require efforts from all levels of healthcare, the data herein presented permits appropriate follow-up for affected individuals and their families. Also, the recognition of risk fac-tors is crucial for planning and implementing preventive measures at the individual and population levels.
Keywords: Cleft Lip; Cleft Palate; Risk Factors; Primary Prevention; Tertiary Prevention.
Introduction
Recognition of etiology, risk factors and natural history is essential to deine how prevention and treatment should be planned and imple-mented, as well as to measure the eficacy of such intervention. These issues, associated with the assessment of outcomes and patient satisfac-tion, form the knowledge base which is critical for developing sensible and equitable healthcare policies.
Oral clefts (OCs) are a heterogeneous and important group of con-genital defects with prevalence of 1:600–1,000 among newborns.1 It in-cludes syndromic and non-syndromic cleft lip (CL), cleft palate (CP) and cleft lip and palate (CLP). OCs are an etiologically heterogeneous group. Approximately 70% of the cases are isolated (non-syndromic) with etio-logic complexity, involving several genetic and environmental risk fac-tors, following a multifactorial threshold model of inheritance. In this situation, familial recurrence is often present and family history should be carefully investigated.
Laboratory facilities have improved the rate of speciic diagnosis, and more than 600 syndromes involving OCs have already been recog-nized.2,3,4,5,6 Mental retardation and association with other congenital defects are often seen in this group, in which chromosomal aberrations are the most frequent etiology. Among them, the 22q11.2 deletion syn-drome deserves special attention, since the phenotype is heterogeneous and changes with age.7
Mendelian/heterogeneous abnormalities and teratogenic factors are the next most prevalent etiologies.8,9,10,11 Teratogenic agents are impor-tant and preventable factors for congenital defects in general.
Submitted: Sep 08, 2013
Accepted for publication: Dec 10, 2013 Last revision: Jan 17, 2014
http://dx.doi.org/10.1590/S1806-83242014.50000008 Epub Feb 12, 2014
Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.
* Paper presented at the “Equity, Social Inclusion and Oral Health Promotion: Major Challenges” International Symposium, Held at the 18th Congress of the Brazilian
Despite all the available technologies, around 50% of patients with syndromic OCs represent cases of multiple congenital anomalies without any identi-iable etiological factor.6,8,9,10,11
The World Health Organization (WHO)12 ac-knowledges that OCs require investment in public policies, in view of their high prevalence, their as-sociation with other congenital defects and co-mor-bidities and their need for prolonged treatment that requires efforts from all levels of healthcare.
Considering the potential for prevention at the population and individual levels, this article de-scribes general aspects of risk factors and particu-larities of the management of OCs.
Prevention
In OCs, the preventive approach can be related to two different strategies:
• education of the population about risk factors and
• genetic counseling for families (or individuals) at risk.
Most risk factors can be recognized during fam-ily planning and prenatal consultations. Families who receive diagnosis and guidance before or dur-ing the prenatal period have the opportunity to seek information and treatment earlier.13
The common risk factors are discussed below.
Lifestyle, maternal illness, nutrition and environmental factors
With regard to OCs, maternal exposure to tobac-co and altobac-cohol use, metabolic status (diabetes, obe-sity or low weight), viral infection, medicinal drugs (anticonvulsants) and teratogens (solvents, agricul-tural chemicals), as well as the preventive role of vi-tamin supplements, have been investigated. Maternal smoking during pregnancy is consistently linked with increased risk of OCs, and second-hand smoking has been investigated as well. Findings on the other risk factors and gene-environment interactions have been inconclusive due to methodological issues.3,4,5
In order to educate the population and health professionals, recommendations for healthy preg-nancies have been made.14,15
Parental age
A meta-analysis approach of parental age showed that fathers 40 years or older have a 58% higher probability of having a child with cleft palate (CP); for mothers over 40 years of age, the probabil-ity is 28% higher for CP and 56% higher for CLP.16
Consanguinity and recurrence
It has been suggested that there is a greater ge-netic component in the etiology of CL based on the observation of an excess of individuals with CL over CLP in the offspring of consanguineous parents.17
A population-based study conducted in Den-mark showed that anatomical severity does have an effect on recurrence in irst-degree relatives, and the type of cleft is predictive of the recurrence type. Third-degree relatives also have an increased recur-rence risk compared to the background population.2 Genetic evaluation and counseling is needed for virtually all patients with OCs because of its het-erogeneous etiology and signiicant association with minor and major defects.5,18 Furthermore, the importance of accurate and detailed phenotype de-scriptions of OCs to produce good etiological and epidemiological studies has recently been empha-sized. In this regard, attention should be given to subphenotypic features of the lip (completeness of the cleft, presence of pits/prints, dental and orbicu-laris oris muscle anomalies) and palate (complete-ness of the cleft, submucous defects, biid uvula and ankyloglossia).3
Also, identiication of the etiology of a syndrom-ic OC would help management of the patient and prevention for the entire family.
Clinical management
Specialized treatment
Multidisciplinary specialized care has been con-sidered state of the art for treatment of OCs.1 It is long-lasting and dependent on surgical correction. When postponed, it increases morbidity and impairs the child’s development.13,19 In addition, orthodon-tics and speech therapy are usually indicated, de-pending on the severity of the cleft.
tis, pneumonia, oral communication disorders and otologic and/or hearing disorders. Emotional and social disturbances are signiicant and deserve atten-tion from both families and health professionals.37
Associated defects
Prevalence of structural defects in association with OC ranges from 8% to 75%, and the majority of reports show that CP has the highest and CL the lowest rates. The orofacial region and cardiovascu-lar, central nervous, and musculoskeletal (including limbs, hands and feet) systems are most commonly involved. Although there are true population differ-ences, methodological factors such as sample source and size, method of ascertainment, inclusion crite-ria, coding system and case classiication account for much of this wide variation.4,9,11,18,38,39,40,41,42,43,44
Management by unspecialized
health professionals
Understanding of the needs and particulari-ties of individuals with OC by health professionals is very important, especially considering the high prevalence of this congenital defect. Nevertheless, health professionals’ knowledge of OC is relatively low.13,28,29,30,32,33
Primary care is an excellent opportunity to rein-force, encourage and monitor dietary guidelines, as well as to prevent co-morbidities. However, it has been observed that healthcare professionals are un-aware of how to manage individuals with OC.33
A study involving Brazilian students during their last academic year for different health professions detected that their knowledge of OC was not sys-tematized. In addition, in self-evaluations, 96.4% afirmed that they were not able to perform routine follow-up of an individual with OC in their own area of expertise. This data has not yet been pub-lished, but the authors are working on suggestions of topics to be used for training.
Discussion
OCs require efforts from all levels of healthcare in view of their high prevalence, their association with other congenital defects and co-morbidities and their need for prolonged treatment. In view of of other congenital defects, co-morbidities and
nu-tritional failure.
Feeding difficulties
Insuficient suction, regurgitation of milk into the nasal cavity, ingestion of insuficient amounts of food and, in special situations, aspirations are described for babies with OC.20,21 These disorders need to be addressed quickly to ensure that nutri-tional needs are met and to avoid or minimize the related complications.1,22
Feeding should promote eficient caloric support for growth and development and for appropriate weight gain for surgical correction at the expected time.23,24 Recommendations and reviews have been published regarding methods and resources for dif-ferent types of cleft.22,25,26,27 Notwithstanding, inad-equate feeding is still a common problem.13,24,28,29,30,31 A high rate of adherence to appropriate feeding and adequate growth is related to systematic moni-toring of patients.31 The lack of follow-up after ma-ternity discharge is particularly relevant and is re-lected in nutritional problems.26,28,29,30,32 The data indicates the need for public policies for longitudi-nal follow-up for babies with OC in primary care.26
Nutrition
Several reports emphasize the importance of the nutritional aspects related to postponement of OC surgical repair.13,28,29,32,33 Mainly, low weight gain and anemia, which should be preventable.34
Although there are reports in the literature on the possibility of breastfeeding with any type of cleft, studies with adequate levels of evidence show that, unlike isolated CL, many patients with CP or CLP can only get breast milk through pumping methods.35,36
The nutritional approach is essential for planning treatment. Orientation regarding feeding methods at birth and longitudinal follow-up are important. The encouragement of breastfeeding and, when that is not possible, the use of breast milk and the preven-tion and treatment of anemia should be priorities.34
Co-morbidities
oti-the complexity of this congenital defect, it has been a challenge to deal with the special needs of individ-uals with OC during routine healthcare assistance. This is a global problem recognized by the WHO.12
This article is intended to help all health profes-sionals understand this complex scenario and pro-vide directions from different perspectives, which could be useful during clinical management.
Recognition of the risk factors and particu-lar health needs of individuals with OC allows the provision of appropriate healthcare. This includes identiication of risk factors, preconceptional and prenatal orientation, neonatal assistance for feeding, investigation of associated congenital defects, and follow-up at the primary care level for monitoring of nutrition and prevention of co-morbidities. This approach facilitates specialized treatment at the right time and may decrease the burden of this prevalent congenital defect.
Conclusion
All the risk factors herein described can be iden-tiied and orientation can be offered during routine consultations. In addition, clinical management from birth can be improved with knowledge of all related aspects. To this end, training of health pro-fessionals should be emphasized.
Acknowledgements
This article was supported by FAPESP - Funda-ção de Amparo à Pesquisa do Estado de São Pau-lo (2003/08959-3) and CNPq - Conselho Nacio-nal de Desenvolvimento Cientíico e Tecnológico
(149600/2010-0), FAPEAL - Fundação de Amparo
à Pesquisa do Estado de Alagoas and Fundo de
Apoio ao Ensino, à Pesquisa e Extensão -
FAE-PEX-UNICAMP. VLGSL is supported by CNPq (304455/2012-1).
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